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Cited by 29Attention Deficit Hyperactivity DisorderThyroid Disorders and TreatmentsNeurotransmitter Receptor Influence on Behavior

Aberrant Monoaminergic System in Thyroid Hormone Receptor-β Deficient Mice as a Model of Attention-Deficit/Hyperactivity Disorder

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Ookubo, Masanori, Sadamatsu, Miyuki, Yoshimura, Atsushi, Suzuki, Satoru, Kato, Nobumasa, Kojima, Hideto, Yamada, Naoto, Kanai, Hirohiko·2015·International Journal of Neuropsychopharmacology
DOI 10.1093/ijnp/pyv004PMC PMC4540106
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Abstract

BACKGROUND: Thyroid hormone receptors are divided into 2 functional types: TRα and TRβ. Thyroid hormone receptors play pivotal roles in the developing brain, and disruption of thyroid hormone receptors can produce permanent behavioral abnormality in animal models and humans. METHODS: Here we examined behavioralchanges, regional monoamine metabolism, and expression of epigenetic modulatory proteins, including acetylated histone H3 and histone deacetylase, in the developing brain of TRα-disrupted (TRα (0/0) ) and TRβ-deficient (TRβ (-/-) ) mice. Tissue concentrations of dopamine, serotonin (5-hydroxytryptamine) and their metabolites in the mesocorticolimbic pathway were measured. RESULTS: TRβ (-/-) mice, a model of attention-deficit/hyperactivity disorder, showed significantly high exploratory activity and reduced habituation, whereas TRα (0/0) mice showed normal exploratory activity. The biochemical profiles of dopamine and 5-hydroxytryptamine showed significantly low dopamine metabolic rates in the caudate putamen and nucleus accumbens and overall low 5-hydroxytryptamine metabolic rates in TRβ (-/-) mice, but not in TRα (0/0) mice. Furthermore, the expression of acetylated histone H3 was low in the dorsal raphe of TRβ (-/-) mice, and histone deacetylase 2/3 proteins were widely increased in the mesolimbic system. CONCLUSIONS: These findings suggest that TRβ deficiency causes dysfunction of the monoaminergic system, accompanied by epigenetic disruption during the brain maturation process.

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  • Dopamine turnover rates are reduced in the NAc of TRβ -/- mice and in mice with perinatal hypothyroidism.

    “Whereas dopamine turnover rates are reduced in the NAc of TRβ -/- mice (35) and in mice with perinatal hypothyroidism (36)”

    From Treatment Preferences in Patients With Hypothyroidism (2025) · cites this paper as [35]

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Cited by

Sorted by citations

Authors
Ookubo, M., Sadamatsu, M., Yoshimura, A., Suzuki, S., Kato, N., Kojima, H., Yamada, N., & Kanai, H.
Affiliations
SHOWA Medical University (JP)
Corresponding author
Kanai, Hirohiko
ORCID
Venue
International Journal of Neuropsychopharmacology
Publisher
Oxford University Press (OUP)
Published
2015-03-20
Volume
18
Issue
7
Pages
pyv004-pyv004
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
DOI
10.1093/ijnp/pyv004
PMC
PMC4540106
OpenAlex
W2043019555
Cited by
29
References
0
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 1
FWCI
1.90
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • The International Journal of Neuropsychopharmacology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
Japan Society for the Promotion of Science (20591364)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
thyroid hormone receptor beta, attention deficit hyperactivity disorder, monoaminergic systems, dopamine metabolism, serotonin metabolism, mesocorticolimbic pathway, acetylated histone H3, epigenetic regulation, brain development, dorsal raphe nucleus, caudate-putamen, nucleus accumbens, exploratory activity, habituation
MeSH terms
Animals, Attention Deficit Disorder with Hyperactivity, Behavior, Animal, Brain, Disease Models, Animal, Dopamine, Exploratory Behavior, Habituation, Psychophysiologic, Histone Deacetylases, Histones, Limbic System, Male, Mice, Inbred C57BL, Nucleus Accumbens, Putamen, Serotonin, Biogenic Monoamines, Signal Transduction, Mice, Knockout, Thyroid Hormone Receptors beta, Mice, Dorsal Raphe Nucleus

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